The prevalence of obesity in children has increased dramatically in recent years. However, conventional treatment has had poor long-term effectiveness. The short-term goal of this competitive renewal application is to provide protected time for the Principal Investigator, David Ludwig, MD, PhD, for an additional 5 years of mentoring and patient-oriented research. During the first period of support, Dr. Ludwig had primary responsibility for the training of 10 full-time graduate students, post-doctoral fellows and junior faculty. In addition, he supervised 14 other individuals for research rotations or career development. A total of 34 scientific articles (including 17 original research studies) were published during the first 4 years of the award period, with additional articles submitted or in preparation. Two new R01 grants were obtained during the initial award period that, together with other ongoing or available studies, provide outstanding opportunities for training junior investigators. The long-term mentoring goal of this project is to help train clinical scientists in the areas of pediatric obesity and nutrition by providing opportunities at all levels (undergraduate, medical student, resident, fellow and junior faculty) to work on state-of-the-art clinical research. The long-term scientific goals are to explore the effects of specific dietary factors on body weight regulation and risk for type 2 diabetes and heart disease, and use these findings to design more effective approaches to obesity treatment and chronic disease prevention. The specific dietary factors of interest include macronutrient composition, glycemic index, fiber, dairy, beverage consumption, food processing and prenatal diet. Toward this end, we will employ controlled feeding study (Specific Aim #1), behaviorally-oriented outpatient clinical trials (Specific Aim #2) and prospective observational analyses (Specific Aim #3). The research environment is ideal to support these goals, including the presence of the Harvard CTSA (""""""""The Catalyst""""""""), the recent establishment of the Obesity Prevention Center at Boston Children's Hospital, the existence of numerous institutional training grants, outstanding access to patients and clinical materials, and an exciting intellectual environment with clinical and basic investigators working in related areas.

Public Health Relevance

Childhood obesity threatens to shorten life-expectancy in the US and cost tax-payers many trillions of dollars over the next few decades. To prevent this potentially catastrophic financial and human toll, novel approaches to the prevention and treatment of obesity are needed, and the next generation of patient oriented researchers with expertise in pediatric obesity must be trained. This application will support the ability of David Ludwig, MD, PhD, a midcareer clinician-scientist, to continue and accelerate mentoring and clinical research in this area.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Midcareer Investigator Award in Patient-Oriented Research (K24)
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Digestive Diseases and Nutrition C Subcommittee (DDK)
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Podskalny, Judith M,
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Children's Hospital Boston
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Ebbeling, Cara B; Klein, Gloria L; Luoto, Patricia K et al. (2018) A randomized study of dietary composition during weight-loss maintenance: Rationale, study design, intervention, and assessment. Contemp Clin Trials 65:76-86
Lennerz, Belinda S; Barton, Anna; Bernstein, Richard K et al. (2018) Management of Type 1 Diabetes With a Very Low-Carbohydrate Diet. Pediatrics 141:
Astley, Christina M; Todd, Jennifer N; Salem, Rany M et al. (2018) Genetic Evidence That Carbohydrate-Stimulated Insulin Secretion Leads to Obesity. Clin Chem 64:192-200
Ludwig, David S (2018) Epidemic Childhood Obesity: Not Yet the End of the Beginning. Pediatrics 141:
Ludwig, David S; Ebbeling, Cara B (2018) The Carbohydrate-Insulin Model of Obesity: Beyond ""Calories In, Calories Out"". JAMA Intern Med 178:1098-1103
Litman, Ethan A; Gortmaker, Steven L; Ebbeling, Cara B et al. (2018) Source of bias in sugar-sweetened beverage research: a systematic review. Public Health Nutr 21:2345-2350
Ebbeling, Cara B; Young, Ian S; Lichtenstein, Alice H et al. (2018) Dietary Fat: Friend or Foe? Clin Chem 64:34-41
Ludwig, David S; Willett, Walter C; Volek, Jeff S et al. (2018) Dietary fat: From foe to friend? Science 362:764-770
Hron, Bridget M; Ebbeling, Cara B; Feldman, Henry A et al. (2017) Hepatic, adipocyte, enteric and pancreatic hormones: response to dietary macronutrient composition and relationship with metabolism. Nutr Metab (Lond) 14:44
Shukla, Alpana P; Andono, Jeselin; Touhamy, Samir H et al. (2017) Carbohydrate-last meal pattern lowers postprandial glucose and insulin excursions in type 2 diabetes. BMJ Open Diabetes Res Care 5:e000440

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